Multitubular enzyme reactors were prepared with immobilized phenylalanine degrading enzymes. Suchenzyme reactors effectively reduced phenylanlanine levels in minutes when tested in vitro and in vivo. There were no adverse physiological effects in the first hours of application in dogs and monkeys rendered temporarily phenylketonuric with high dietary levels of phenylalanine. We plan to further improve the reactors and to employ phenylalanine hydroxylase of mamalian origin instead of phenylalanine-ammonia-lyase of plant or yeast origin used this far. We will also try to immobilize on the same reactors plasminogen activators (streptokinase and urokinase) in order to reduce the need for heparinization. We will test the in vitro and in vivo efficacy on the best types produced. Studies on in vivo safely of the reactors will include evaluation of immunogenicity upon repeated application. These studies should lead to eventual clinical exploration of reactors in various types of phenylketonuric patients.